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What a fantastic thing that would be if a diseased organ could be quickly and easily replaced by a new one designed individually for a specific person or if a new drug could be tested on an artificial organ system made of living cells instead of using thousands of animals! Although all this may seem like science fiction at first glance, the rapidly developing world of biotechnology has already made this reality.

In the past 20 years, scientists have made a global breakthrough in organ and tissue engineering. We have already partly discussed this in the paper on in vitro technologies. This article provides a more detailed overview of the creation of artificial organs and their applications for scientific purposes.


“Organs-on-chips” The integrated system shown is composed of a “brain on a chip” (middle), “breast cancer model on a chip” (right), and a device for metabolic measurements (left). The system was designed to study breast cancer metastasis in the brain. From reference [1].

Engineered tissues are extensively used in medical research today. Some projects of the kind are still under clinical testing. Of course, such “organs” are still much simpler in their architecture than the real ones. For instance, modern technologies have facilitated the construction of a stomach prototype from relevant cells. However, because of missing in blood vessels, nerves or interaction with other organs, such an organ resembles a stomach-shaped “statue” incapable of digestion and gurgling. In fact, an organ is far more than just a set of specific cells arranged in a certain order. However, despite all the challenges, scientists are not giving up on addressing the problem of creating artificial organs from multiple angles.

Generating a working organ replica is a complicated task. One of the approaches to solving this problem is modeling their properties and functions instead. So-called “organs-on-chips”1 have now gained wide application in various scientific areas. Compartments to accommodate multiple types of human cells are produced in a small clear matrix plate and are connected by channels – blood or lymphatic “vessels”. The multiple cell types seeded mimic various organs and tissues. The chip is placed in a special reactor, which maintains optimal conditions for the culture solution to circulate through the “vessels”, modeling blood flow.1 Today researchers can use different approaches to generating mechanical, chemical, and electrical signals that are typical for certain states of the organism. For instance, this type of system can be used to model the inflammatory process by adding pro-inflammatory agents (cytokines) or immune cells2. The chip is designed to acquire information on the organ’s state in real time and at high resolution. “Organs-on-chips” are already in broad use throughout the world, helping tackle numerous scientific challenges. This strategy of reproducing parts of the human body provides convenience in studying the functions and pathology of real-life organs as well as in drug testing1.

To date, there are organ-on-chip simulants for the liver, kidney, lung, intestine, muscle, adipose tissue, and the blood-brain barrier.3-7 Furthermore, scientists are now using these organs to produce integrated systems, such as liver-kidney or heart-liver-blood circulation1,6-7. In 2018, a “body-on-a-chip”(a human body model) was developed. It contains 10 organs and tissues: the liver, kidney, pancreas, intestine, heart, lung, brain, endometrium, skin and skeletal muscle8. Within this system, a drug can be injected “intravenously”, into “the gut” (“orally”), or onto the skin, with its effects on other organs and tissues being subsequently tracked. Composite “organ-on-chip” systems can enable experiments that, for some reasons, are unfeasible in cell cultures, animals or humans. The above systems can be “individually tailored”, i.e. fabricated from a specific patient’s cells, facilitating a more detailed and extended (in time) measurement of the patient’s unique physiological characteristics.1 This approach is bringing us closer to personalized medicine of the future. There are already a number of laboratory-based companies manufacturing commercial “organs-on-chips”, mainly for the needs of drug screening and toxicity testing1.

First attempts at creating artificial organs that mimic real ones in structure and shape date back to the end of the previous century. One of the initial strategies used was regenerating the structure of an organ (e.g. the ear) from a biodegradable polymer scaffold into which organ-specific cells (e.g. cartilaginous cells) were then seeded. Over time, the cells invade and degrade the scaffold. Making this approach work requires a special environment. Initial projects utilized host animals as a kind of bioreactor to grow such organs. This was the technique used to create the famous earmouse9. By applying similar bioreactor techniques, scientists have been able to produce and make clinical use of relatively simple organs such as the bladder, blood vessels, urethra, and the vagina10-12. Importantly, such artificial organs can be “grown” from the patient’s own cells, preventing the risk of rejection.

In the 21st century, bioengineers began to take advantage of 3D printing technology, where various living cells serve as the “ink” and special biocompatible gel materials are used as the paper13. 3D printed constructs are then transferred to a special incubator to allow them to grow and mature. This technology can currently help reproduce rather detailed models of the skin, cartilage, heart valves, vessels, and liver tissue14-17. However, there has been less success in fabricating complex organs. Scientists today can only print their mini-replicas – organoids. So far there have been 3D printed organoids mimicking the intestine, brain, liver, kidney, mammary gland and the thyroid13,18-20. Yet a trickier challenge for scientists is introducing the complex vascular system in an organ being constructed, for example, an attempt at modeling the heart. Nevertheless, a sort of cardiac patches (pieces of vascularized heart tissue) have been printed to date and used successfully in clinical settings21. Most recently, functioning miniature models of the heart and lung containing complex vascular networks have been successfully printed.21-23

Some groups of scientists have chosen a different path by employing the natural potential of living systems to self-organize. As it turned out, stem cells grown in a certain environment can transform into various cell types and aggregate into complex organ-like structures (called organoids again)1. Organoids are generally much smaller than the naturally occurring organs and have a far simpler structure. These days, intestine, kidney and retina organoids have been produced. Researchers are currently working at generating organoids that model complex organs, such as the brain, first models of which of the size of a lentil are even available so far23.

However, as with other in vitro organs, the central problem here is the lack of blood vessels and interaction with other structures. Over time (after a maximum of 12 months), organoids begin to lose resemblance to their prototypes and die. In addition to this, it is still a challenge to build organoids with consistently similar properties. The unpredictable self-assembly process results in particles varying in shape from batch to batch24.

Whichever way of reproducing in vitro organs researchers might select, what ultimately matters is the functionality of the tool produced. Perfect likeness between a generated organ and the original is not always necessary. Artificially created human tissues and organoids are highly helpful in efficacy and safety evaluations of drugs and cosmetics24. Their use sufficiently reduces the duration and cost of testing new pharmaceuticals, enhancing reliability and ethicality. Tissue engineering technologies have also been applied to clinical practice, moving us towards personalized medicine. Whether it be a cardiac patch, toxicity test or stem cell organoid1 for exploring brain diseases, organ and tissue manufacturing technologies can provide scientists with the most vital thing – the opportunity to help people.


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13.    https://www.ted.com/talks/anthony_atala_printing_a_human_kidney/

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18.    https://www.sciencedaily.com/releases/2017/12/171206122609.htm

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24.    https://www.bbc.com/news/technology-32795169